Transformer-based AI approach to unravel long-term, time-dependent prognostic complexity in patients with advanced NSCLC and PD-L1 ≥50%: insights from the pembrolizumab 5-year global registry
| Title: | Transformer-based AI approach to unravel long-term, time-dependent prognostic complexity in patients with advanced NSCLC and PD-L1 ≥50%: insights from the pembrolizumab 5-year global registry |
|---|---|
| Authors: | Cortellini, Alessio; Santo, Valentina; Brunetti, Leonardo; Garbo, Edoardo; Pinato, David J; La Cava, Giulia; Naidoo, Jarushka; Katz, Artur; Loza, Monica; Neal, Joel W; Genova, Carlo; Gettinger, Scott; Kim, So Yeon; Jayakrishnan, Ritujith; El Zarif, Talal; Russano, Marco; Pecci, Federica; Di Federico, Alessandro; Alessi, Joao V; Montrone, Michele; Owen, Dwight H; Ramella, Sara; Signorelli, Diego; Fidler, Mary Jo; Li, Mingjia; Camerini, Andrea; Halmos, Balazs; Vincenzi, Bruno; Metro, Giulio; Passiglia, Francesco; Yendamuri, Sai; Guida, Annalisa; Ghidini, Michele; D'Alessio, Antonio; Banna, Giuseppe L; Fulgenzi, Claudia A M; Grisanti, Salvatore; Grossi, Francesco; D'Incecco, Armida; Josephides, Eleni; Van Hemelrijck, Mieke; Russo, Alessandro; Gelibter, Alain; Spinelli, Gianpaolo; Verrico, Monica; Tomasik, Bartłomiej; Giusti, Raffaele; Balachandran, Kirsty; Bria, Emilio; Sebastian, Martin; Rost, Maximilian; Forster, Martin; Mukherjee, Uma; Landi, Lorenza; Mazzoni, Francesca; Aujayeb, Avinash; Dupont, Manuel; Curioni-Fontecedro, Alessandra; Chiari, Rita; Sforza, Vincenzo; Tiseo, Marcello; Friedlaender, Alex; Addeo, Alfredo; Zoratto, Federica; De Tursi, Michele; Cantini, Luca; Roca, Elisa; Mountzios, Giannis; Rocco, Danilo; Della Gravara, Luigi; Kalvapudi, Sukumar; Inno, Alessandro; Bironzo, Paolo; Di Marco Barros, Rafael; O'Reilly, David; Fitzpatrick, Orla; Karapanagiotou, Eleni; Monnet, Isabelle; Baena, Javier; Macerelli, Marianna; Piedra, Aida; Agustoni, Francesco; Cortinovis, Diego Luigi; Tonini, Giuseppe; Minuti, Gabriele; Bennati, Chiara; Mezquita, Laura; Gorría, Teresa; Servetto, Alberto; Beninato, Teresa; Lo Russo, Giuseppe; Prelaj, Arsela; De Giglio, Andrea; Rogado, Jacobo; Moliner, Laura; Nadal, Ernest; Biello, Federica; Nana, Frank Aboubakar; Dingemans, Anne-Marie; Aerts, Joachim G J V; Ferrara, Roberto; Abu Hejleh, Taher; Takada, Kazuki; Naqash, Abdul Rafeh; Garassino, Marina Chiara; Peters, Solange; Wakelee, Heather A; Nassar, Amin H; Ricciuti, Biagio; Soda, Paolo; Caruso, Camillo Maria; Guarrasi, Valerio |
| Contributors: | Cortellini, A; Santo, V; Brunetti, L; Garbo, E; Pinato, D; La Cava, G; Naidoo, J; Katz, A; Loza, M; Neal, J; Genova, C; Gettinger, S; Kim, S; Jayakrishnan, R; El Zarif, T; Russano, M; Pecci, F; Di Federico, A; Alessi, J; Montrone, M; Owen, D; Ramella, S; Signorelli, D; Fidler, M; Li, M; Camerini, A; Halmos, B; Vincenzi, B; Metro, G; Passiglia, F; Yendamuri, S; Guida, A; Ghidini, M; D'Alessio, A; Banna, G; Fulgenzi, C; Grisanti, S; Grossi, F; D'Incecco, A; Josephides, E; Van Hemelrijck, M; Russo, A; Gelibter, A; Spinelli, G; Verrico, M; Tomasik, B; Giusti, R; Balachandran, K; Bria, E; Sebastian, M; Rost, M; Forster, M; Mukherjee, U; Landi, L; Mazzoni, F; Aujayeb, A; Dupont, M; Curioni-Fontecedro, A; Chiari, R; Sforza, V; Tiseo, M; Friedlaender, A; Addeo, A; Zoratto, F; De Tursi, M; Cantini, L; Roca, E; Mountzios, G; Rocco, D; Della Gravara, L; Kalvapudi, S; Inno, A; Bironzo, P; Di Marco Barros, R; O'Reilly, D; Fitzpatrick, O; Karapanagiotou, E; Monnet, I; Baena, J; Macerelli, M; Piedra, A; Agustoni, F; Cortinovis, D; Tonini, G; Minuti, G; Bennati, C; Mezquita, L; Gorría, T; Servetto, A; Beninato, T; Lo Russo, G; Prelaj, A; De Giglio, A; Rogado, J; Moliner, L; Nadal, E; Biello, F; Nana, F; Dingemans, A; Aerts, J |
| Publisher Information: | BMJ Publishing Group; GB |
| Publication Year: | 2025 |
| Collection: | Università degli Studi di Milano-Bicocca: BOA (Bicocca Open Archive) |
| Subject Terms: | Immune Checkpoint Inhibitor; Immunotherapy; Lung Cancer; Survivorship |
| Description: | Background With nearly one-third of patients with advanced non-small cell lung cancer (NSCLC) and PD-L1 Tumor Proportion Score≥50% surviving beyond 5 years following first-line pembrolizumab, long-term outcomes challenge traditional paradigms of cancer prognostication. The emergence of non-cancer-related factors and time-dependent trends underscores the need for advanced analytical frameworks to unravel their complex interplay. Methods We analyzed the Pembro-real 5Y registry, a global real-world dataset of 1050 patients treated across 61 institutions in 14 countries with a long-term follow-up and a large panel of baseline variables. Two complementary approaches were employed: ridge regression, chosen for its ability to address multicollinearity while retaining interpretability, and not another imputation method (NAIM), a transformer-based artificial intelligence model designed to handle missing data without imputation. Endpoints included risk of death at 6, 12, 24, 60 months and 5-year survival. Results The ridge regression model achieved a c-statistic of 0.66 (95% CI: 0.59 to 0.72) for the risk of death and an area under the curve (AUC) of 0.72 (95% CI: 0.65 to 0.78) for 5-year survival, identifying Eastern Cooperative Oncology Group Performance Status (ECOG-PS)≥2, increasing age, and metastatic burden as primary risk factors. However, wide CIs for some predictors highlighted statistical instability. NAIM demonstrated robust handling of missing data, with a c-index of 62.98±2.11 for risk of death and an AUC of 60.52±3.71 for 5-year survival. The comprehensive SHapley Additive exPlanations analysis revealed dynamic, time-dependent patterns, with early mortality dominated by acute factors (eg, ECOG-PS, steroids) and long-term outcomes increasingly influenced by systemic health markers (eg, absence of hypertension, increasing body mass index). Unexpected insights included the protective role of dyslipidemia (but not statins) and the nuanced impact of smoking status, reflecting evolving disease dynamics and ... |
| Document Type: | article in journal/newspaper |
| File Description: | ELETTRONICO |
| Language: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/41022528; info:eu-repo/semantics/altIdentifier/wos/WOS:001615592000001; volume:13; issue:9; journal:JOURNAL FOR IMMUNOTHERAPY OF CANCER; https://hdl.handle.net/10281/576081 |
| DOI: | 10.1136/jitc-2025-012423 |
| Availability: | https://hdl.handle.net/10281/576081; https://doi.org/10.1136/jitc-2025-012423 |
| Rights: | info:eu-repo/semantics/openAccess ; license:Creative Commons ; license uri:http://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: | edsbas.30823A1E |
| Database: | BASE |